Profiling cognitive-motor interference in a large sample of persons with progressive multiple sclerosis and impaired processing speed: results from the CogEx study.

BACKGROUND: Performing cognitive-motor dual tasks (DTs) may result in reduced walking speed and cognitive performance. The effect in persons with progressive multiple sclerosis (pwPMS) having cognitive dysfunction is unknown. OBJECTIVE: To profile DT-performance during walking in cognitively impaired pwPMS and examine DT-performance by disability level. METHODS: Secondary analyses were conducted on baseline data from the CogEx-study. Participants, enrolled with Symbol Digit Modalities Test 1.282 standard deviations below normative value, performed a cognitive single task ([ST], alternating alphabet), motor ST (walking) and DT (both). Outcomes were number of correct answers on the alternating alphabet task, walking speed, and DT-cost (DTC: decline in performance relative to the ST). Outcomes were compared between EDSS subgroups (≤ 4, 4.5-5.5, ≥ 6). Spearman correlations were conducted between the DTCmotor with clinical measures. Adjusted significance level was 0.01. RESULTS: Overall, participants (n = 307) walked slower and had fewer correct answers on the DT versus ST (both p < 0.001), with a DTCmotor of 15.8% and DTCcognitive of 2.7%. All three subgroups walked slower during the DT versus ST, with DTCmotor different from zero (p's < 0.001). Only the EDSS ≥ 6 group had fewer correct answers on the DT versus ST (p < 0.001), but the DTCcognitive did not differ from zero for any of the groups (p ≥ 0.039). CONCLUSION: Dual tasking substantially affects walking performance in cognitively impaired pwPMS, to a similar degree for EDSS subgroups.

Is the Goligher classification a valid tool in clinical practice and research for hemorrhoidal disease?

BACKGROUND: The most widely used classification for hemorrhoidal disease (HD) is the Goligher classification, which ranks presence and severity of prolapse in four grades. Since physicians base this gradation on medical history and physical examination, it might be prone to interobserver variability. Furthermore, the gradation impacts the treatment of choice which makes reproducibility of utmost importance. The aim of this study was to determine the interobserver variability of Goligher classification among surgeons in the Netherlands. METHODS: A single-choice survey was used. The first part consisted of questions concerning baseline characteristics and the use of the Goligher classification in routine clinical practice. In the second part, to assess interobserver variability, we asked gastrointestinal surgeons and residents who routinely treat HD to review 25 photographs (with given timing as during rest or push) of patients with HD and classify the gradation using the Goligher classification. The survey was sent by email on April 19, 2021 and was available online until July 5, 2021. Interobserver variability was assessed using Fleiss' Kappa test. RESULTS: A total of 329 gastrointestinal surgeons, fellows and residents were sent an invitation email, of whom 95 (29%) completed the survey. Among the respondents, 87% indicated that they use the Goligher classification in clinical practice. Eighty-one percent found the classification helpful and 63% classified HD according to Goligher and followed the guidelines for treatment of HD accordingly. The interobserver variability showed an overall fair strength of agreement, with a Fleiss' Kappa (κ) of 0.376 (95% CI 0.373-0.380). There was a moderate agreement for grade I and IV HD with a κ statistic of 0.466 and 0.522, respectively. For grades II and III, there was a lower (fair) strength of agreement with 0.206 and 0.378, respectively. CONCLUSIONS: The fair interobserver variability is disappointing and demonstrates the need for a more reliable, and internationally accepted, classification for HD. A new classification should enable more uniformity in treating HD and in comparing outcomes of future trials and prospective registries. The protocol for a Delphi study for a new classification system is currently being prepared and led by an international research group.

Associations between clinical characteristics and dual task performance in Multiple Sclerosis depend on the cognitive and motor dual tasks used.

BACKGROUND: In persons with Multiple Sclerosis (pwMS) performing a simultaneous cognitive task while walking often results in slower gait. Clinical characteristics associated with reduced dual task (DT) performance are not yet entirely clear. This multi-centre study aimed to determine the relationship between clinical and demographical characteristics with dual task (DT) walking performance in pwMS during multiple DT conditions. METHODS: Nine DT conditions were analysed, consisting of combinations of three types of cognitive ('digit span', 'subtraction', 'vigilance') and three types of walking ('walk', 'walk with cup', 'walk over obstacles') conditions. Primary outcomes were DT gait speed (m/s) and motor DT cost of gait speed (DTCmotor, %). Secondary outcomes were clinical tests of physical and cognitive functioning and patient-reported and demographical outcomes. Firstly, univariate analyses and, subsequently, multivariate analyses with backward modelling, were conducted for each type of walking DT condition separately. Cognitive DT conditions were included in the models as main and as interaction effect with the secondary outcomes. RESULTS: Analysis were performed in 81 pwMS (EDSS 3.3 ± 1.0). In the final models of DTCmotor, the significant main effects were in 'walk' DT-conditions the Symbol Digit Modalities Test (SDMT), in 'cup' conditions the SDMT and Dynamic Gait Index and in 'obstacles' conditions age. For DT gait speed, main effects were found for the 2-Minute Walking Test (2MWT) and the Multiple Sclerosis Walking Scale for all walking conditions. Additionally, interactions between cognitive DT-conditions and SDMT, age and 2MWT were found. CONCLUSION: Clinical characteristics related to DT walking performance differed according to cognitive-motor DT-condition used. Still, in general, pwMS with a better mobility demonstrated higher DT gait speed, while a faster information processing speed was related to a lower DTCmotor.

A Dutch MYH7 founder mutation, p.(Asn1918Lys), is associated with early onset cardiomyopathy and congenital heart defects.

BACKGROUND: Mutations in the myosin heavy chain 7 (MYH7) gene commonly cause cardiomyopathy but are less frequently associated with congenital heart defects. METHODS: In this study, we describe a mutation in the MYH7 gene, c. 5754C > G; p. (Asn1918Lys), present in 15 probands and 65 family members. RESULTS: Of the 80 carriers (age range 0-88 years), 46 (57.5%) had cardiomyopathy (mainly dilated cardiomyopathy (DCM)) and seven (8.8%) had a congenital heart defect. Childhood onset of cardiomyopathy was present in almost 10% of carriers. However, in only a slight majority (53.7%) was the left ventricular ejection fraction reduced and almost no arrhythmias or conduction disorders were noted. Moreover, only one carrier required heart transplantation and nine (11.3%) an implantable cardioverter defibrillator. In addition, the standardised mortality ratio for MYH7 carriers was not significantly increased. Whole exome sequencing in several cases with paediatric onset of DCM and one with isolated congenital heart defects did not reveal additional known disease-causing variants. Haplotype analysis suggests that the MYH7 variant is a founder mutation, and is therefore the first Dutch founder mutation identified in the MYH7 gene. The mutation appears to have originated in the western region of the province of South Holland between 500 and 900 years ago. CONCLUSION: Clinically, the p. (Asn1918Lys) mutation is associated with congenital heart defects and/or cardiomyopathy at young age but with a relatively benign course.

Dormant and after-Ripened Arabidopsis thaliana Seeds are Distinguished by Early Transcriptional Differences in the Imbibed State.

Seed dormancy is a genetically controlled block preventing the germination of imbibed seeds in favorable conditions. It requires a period of dry storage (after-ripening) or certain environmental conditions to be overcome. Dormancy is an important seed trait, which is under selective pressure, to control the seasonal timing of seed germination. Dormant and non-dormant (after-ripened) seeds are characterized by large sets of differentially expressed genes. However, little information is available concerning the temporal and spatial transcriptional changes during early stages of rehydration in dormant and non-dormant seeds. We employed genome-wide transcriptome analysis on seeds of the model plant Arabidopsis thaliana to investigate transcriptional changes in dry seeds upon rehydration. We analyzed gene expression of dormant and after-ripened seeds of the Cvi accession over four time points and two seed compartments (the embryo and surrounding single cell layer endosperm), during the first 24 h after sowing. This work provides a global view of gene expression changes in dormant and non-dormant seeds with temporal and spatial detail, and these may be visualized via a web accessible tool (http://www.wageningenseedlab.nl/resources). A large proportion of transcripts change similarly in both dormant and non-dormant seeds upon rehydration, however, the first differences in transcript abundances become visible shortly after the initiation of imbibition, indicating that changes induced by after-ripening are detected and responded to rapidly upon rehydration. We identified several gene expression profiles which contribute to differential gene expression between dormant and non-dormant samples. Genes with enhanced expression in the endosperm of dormant seeds were overrepresented for stress-related Gene Ontology categories, suggesting a protective role for the endosperm against biotic and abiotic stress to support persistence of the dormant seed in its environment.

A rare stress cardiomyopathy in a patient with Guillain-Barré syndrome.

We report on a 39-year-old woman who was intubated because of progressive respiratory failure due to muscle weakness and mucous plugging because of Guillain- Barré syndrome. Shortly after uncomplicated intubation she developed hypotension and a profound tachycardia. The electrocardiogram showed sinus tachycardia with nonspecific ST-T segment changes. Echocardiography showed akinesia of the apex, septum and inferior left ventricular wall with an estimated left ventricular ejection fraction of 10%. It was concluded that the patient was suffering from takotsubo cardiomyopathy. Following treatment, she experienced a complete recovery. Takotsubo cardiomyopathy is a rare complication in Guillain-Barré syndrome; eight other cases have been reported in the literature.

Transcriptional dynamics of two seed compartments with opposing roles in Arabidopsis seed germination.

Seed germination is a critical stage in the plant life cycle and the first step toward successful plant establishment. Therefore, understanding germination is of important ecological and agronomical relevance. Previous research revealed that different seed compartments (testa, endosperm, and embryo) control germination, but little is known about the underlying spatial and temporal transcriptome changes that lead to seed germination. We analyzed genome-wide expression in germinating Arabidopsis (Arabidopsis thaliana) seeds with both temporal and spatial detail and provide Web-accessible visualizations of the data reported (vseed.nottingham.ac.uk). We show the potential of this high-resolution data set for the construction of meaningful coexpression networks, which provide insight into the genetic control of germination. The data set reveals two transcriptional phases during germination that are separated by testa rupture. The first phase is marked by large transcriptome changes as the seed switches from a dry, quiescent state to a hydrated and active state. At the end of this first transcriptional phase, the number of differentially expressed genes between consecutive time points drops. This increases again at testa rupture, the start of the second transcriptional phase. Transcriptome data indicate a role for mechano-induced signaling at this stage and subsequently highlight the fates of the endosperm and radicle: senescence and growth, respectively. Finally, using a phylotranscriptomic approach, we show that expression levels of evolutionarily young genes drop during the first transcriptional phase and increase during the second phase. Evolutionarily old genes show an opposite pattern, suggesting a more conserved transcriptome prior to the completion of germination.

A prospective validation of the HEART score for chest pain patients at the emergency department.

BACKGROUND: The focus of the diagnostic process in chest pain patients at the emergency department is to identify both low and high risk patients for an acute coronary syndrome (ACS). The HEART score was designed to facilitate this process. This study is a prospective validation of the HEART score. METHODS: A total of 2440 unselected patients presented with chest pain at the cardiac emergency department of ten participating hospitals in The Netherlands. The HEART score was assessed as soon as the first lab results and ECG were obtained. Primary endpoint was the occurrence of major adverse cardiac events (MACE) within 6 weeks. Secondary endpoints were (i) the occurrence of AMI and death, (ii) ACS and (iii) the performance of a coronary angiogram. The performance of the HEART score was compared with the TIMI and GRACE scores. RESULTS: Low HEART scores (values 0-3) were calculated in 36.4% of the patients. MACE occurred in 1.7%. In patients with HEART scores 4-6, MACE was diagnosed in 16.6%. In patients with high HEART scores (values 7-10), MACE occurred in 50.1%. The c-statistic of the HEART score (0.83) is significantly higher than the c-statistic of TIMI (0.75)and GRACE (0.70) respectively (p<0.0001). CONCLUSION: The HEART score provides the clinician with a quick and reliable predictor of outcome, without computer-required calculating. Low HEART scores (0-3), exclude short-term MACE with >98% certainty. In these patients one might consider reserved policies. In patients with high HEART scores (7-10) the high risk of MACE may indicate more aggressive policies.

Identification of reference genes for RT-qPCR expression analysis in Arabidopsis and tomato seeds.

Quantifying gene expression levels is an important research tool to understand biological systems. Reverse transcription-quantitative real-time PCR (RT-qPCR) is the preferred method for targeted gene expression measurements because of its sensitivity and reproducibility. However, normalization, necessary to correct for sample input and reverse transcriptase efficiency, is a crucial step to obtain reliable RT-qPCR results. Stably expressed genes (i.e. genes whose expression is not affected by the treatment or developmental stage under study) are indispensable for accurate normalization of RT-qPCR experiments. Lack of accurate normalization could affect the results and may lead to false conclusions. Since transcriptomes of seeds are different from other plant tissues, we aimed to identify reference genes specifically for RT-qPCR analyses in seeds of two important seed model species, i.e. Arabidopsis and tomato. We mined Arabidopsis seed microarray data to identify stably expressed genes and analyzed these together with putative reference genes from other sources. In total, the expression stability of 24 putative reference genes was validated by RT-qPCR in Arabidopsis seed samples. For tomato, we lacked transcriptome data sets of seeds and therefore we tested the tomato homologs of the reference genes found for Arabidopsis seeds. In conclusion, we identified 14 Arabidopsis and nine tomato reference genes. This provides a valuable resource for accurate normalization of gene expression experiments in seed research for two important seed model species.

Magnetic resonance imaging, pacemakers and implantable cardioverter-defibrillators: current situation and clinical perspective.

New developments and expanding indications have resulted in a significant increase in the number of patients with pacemakers and internal cardioverterdefibrillators (ICDs). Because of its unique capabilities, magnetic resonance imaging (MRI) has become one of the most important imaging modalities for evaluation of the central nervous system, tumours, musculoskeletal disorders and some cardiovascular diseases. As a consequence of these developments, an increasing number of patients with implanted devices meet the standard indications for MRI examination. Due to the presence of potential life-threatening risks and interactions, however, pacemakers and ICDs are currently not approved by the Food and Drug Administration (FDA) for use in an MRI scanner. Despite these limitations and restrictions, a limited but still growing number of studies reporting on the effects and safety issues of MRI and implanted devices have been published. Because physicians will be increasingly confronted with the issue of MRI in patients with implanted devices, this overview is given. The effects of MRI on an implanted pacemaker and/or ICDs and vice versa are described and, based on the current literature, a strategy for safe performance of MRI in these patients is proposed. (Neth Heart J 2010;18:31-7.).

[Partial resistance to acenocoumarol and phenprocoumon caused by enzyme polymorphism]. / Partiële acenocoumarol- en fenprocoumonresistentie door enzympolymorfisme.

A 78-year-old man was treated with coumarin derivatives following myocardial infarction. The international normalised ratio was not increased by using standard loading doses and dose adjustments for acenocoumarol and phenprocoumon. The desired level of anticoagulation was achieved with a high dosage of phenprocoumon (18-21 mg daily). This dose was associated with a phenprocoumon serum concentration that was ten times higher than the normal therapeutic concentration. The serum concentration of vitamin K1 was low. After exclusion of alternative causes, we concluded that the exceptionally high dose of phenprocoumon needed was due to partial resistance to coumarin derivatives. Partial resistance is related to a polymorphism of the gene coding for the enzyme vitamin K epoxide reductase. The patient was successfully treated with chronic high-dose phenprocoumon. Resistance to coumarin derivatives caused by a congenital polymorphism in the vitamin K reductase gene is a rare phenomenon. Resistance is seldom absolute. The desired anticoagulation effect can be achieved with doses that are 10-20 times higher than standard doses. Phenprocoumon is advantageous in this situation because it requires fewer tablets than acenocoumarol. Determination of serum concentrations of acenocoumarol and phenprocoumon can be used to exclude other causes of treatment resistance.

Mural aortic thrombus and peripheral embolisation in a patient with hyperhomocysteinaemia.

A mobile thrombus of the descending thoracic aorta in young people is extremely uncommon. We describe a 38-year-old woman with a mural thrombus in the proximal aorta complicated by peripheral embolisation, due to hyperhomocysteinaemia.

Suspended solids transport: an analysis based on turbidity measurements and event based fully calibrated hydrodynamic models.

Modelling suspended solids transport is a key issue for predicting the pollution load discharged by CSOs. Nonetheless, there is still much debate on the main drivers for suspended solids transport and on the modelling approach to be adopted. Current sewer models provide suspended solids transport models. These models, however, rely upon erosion-deposition criteria developed in fluvial environments, therewith oversimplifying the sewer sediment characteristics. Consequently, the performance of these models is poor from a theoretical point of view. To get an improved understanding of the temporal and spatial variations in suspended solids transport, a measuring network was installed in the sewer system of Loenen in conjunction with a hydraulic measuring network from June through December 2001. During the measuring period, 15 storm events rendered high-quality data on both the hydraulics and the turbidity. For each storm event, a hydrodynamic model was calibrated using the Clemens' method. The conclusion of the paper is that modelling of suspended solids transport has been and will be one of the challenges in the field of urban drainage modelling. A direct relation of either shear stress or flow velocity with turbidity could not be found, likely because of the time varying characteristics of the suspended solids.

Detailed observation and measurement of sewer sediment erosion under aerobic and anaerobic conditions.

A greater understanding of the erosion behaviour of sewer sediments is necessary in order to reliably estimate the amount and nature of the sewer sediments released from deposits in sewers and transported either to waste water treatment plants or discharged into the environment. Research has indicated that microbial activity in sediment can influence the physical release of sediment from in-pipe deposits. This paper reports on a series of erosion tests in which sewer sediments from different sewer networks are kept under different environmental conditions and their resistance to erosion is examined. The erosion tests are carried out under aerobic and anaerobic conditions and two temperatures, one representing ambient sewer temperatures and a lower temperature that significantly suppresses bacterial activity.

Costs and quality of life after endoscopic repair of inguinal hernia vs open tension-free repair: a review.

BACKGROUND: The ongoing debate about the relative merits of endoscopic (EH) vs open mesh herniorrhaphy (OH) prompts the need for comparisons of outcome measures other than recurrence. Therefore, we reviewed data on the costs, time to return to work, quality of life (QoL), and pain associated with EH and OH. METHODS: Studies comparing EH to OH and explicitly involving costs or QoL were identified and reviewed. RESULTS: Eighteen studies were included. Direct in-hospital costs were higher for unilateral EH. Direct out-of-hospital costs were lower after EH in some studies. Indirect costs were lower for EH. Total costs were higher for EH in three studies and lower in one study. With EH, QoL was better, pain was less, operating time was longer, and time return to work and other activities was shorter. CONCLUSION: From a societal perspective, EH entails costs similar to OH but offers extra benefits to the patient in terms of QoL and pain.

Impact of hospital case volume on short-term outcome after laparoscopic operation for colonic cancer.

BACKGROUND: High hospital case volume has been associated with improved outcome after open operation for colorectal malignancies. METHODS: To assess the impact of hospital case volume on short-term outcome after laparoscopic operation for colon cancer, we conducted an analysis of patients who underwent laparoscopic colon resection within the COlon Cancer Laparoscopic or Open Resection (COLOR) trial. RESULTS: A total of 536 patients with adenocarcinoma of the colon were included in the analysis. Median operating time was 240, 210 and 188 min in centers with low, medium, and high case volumes, respectively (p < 0.001). A significant difference in conversion rate was observed among low, medium, and high case volume hospitals (24% vs 24% vs 9%; p < 0.001). A higher number of lymph nodes were harvested at high case volume hospitals (p < 0.001). After operation, fewer complications (p = 0.006) and a shorter hospital stay (p < 0.001) were observed in patients treated at hospitals with high caseloads. CONCLUSIONS: Laparoscopic operation for colon cancer at hospitals with high caseloads appears to be associated with improved short-term results.

Laparoscopic resection of colon Cancer: consensus of the European Association of Endoscopic Surgery (EAES).

BACKGROUND: The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on the laparoscopic resection of colon cancer during the annual congress in Lisbon, Portugal, in June 2002. METHODS: A systematic review of the current literature was combined with the opinions, of experts in the field of colon cancer surgery to formulate evidence-based statements and recommendations on the laparoscopic resection of colon cancer. RESULTS: Advanced age, obesity, and previous abdominal operations are not considered absolute contraindications for laparoscopic colon cancer surgery. The most common cause for conversion is the presence of bulky or invasive tumors. Laparoscopic operation takes longer to perform than the open counterpart, but the outcome is similar in terms of specimen size and pathological examination. Immediate postoperative morbidity and mortality are comparable for laparoscopic and open colonic cancer surgery. The laparoscopically operated patients had less postoperative pain, better-preserved pulmonary function, earlier restoration of gastrointestinal function, and an earlier discharge from the hospital. The postoperative stress response is lower after laparoscopic colectomy. The incidence of port site metastases is <1%. Survival after laparoscopic resection of colon cancer appears to be at least equal to survival after open resection. The costs of laparoscopic surgery for colon cancer are higher than those for open surgery. CONCLUSION: Laparoscopic resection of colon cancer is a safe and feasible procedure that improves short-term outcome. Results regarding the long-term survival of patients enrolled in large multicenter trials will determine its role in general surgery.

Stress response to laparoscopic surgery: a review.

BACKGROUND: Laparoscopic surgery is associated with reduced surgical trauma, and therefore with a less acute phase response, as compared with open surgery. Impairment of the immune system may enhance surgical infections, port-site metastases, and sepsis. The objectives of this review was to assess immunologic consequences of benign laparoscopic surgery and to highlight controversial aspects. METHODS: A literature search on stress response to nonmalignant laparoscopic and open surgery was conducted using the MEDLINE and Cochrane databases. Cross-references from the reference list of major articles on the subject were used, as well as manuscripts published between 1993 and 2002. RESULTS: Local (i.e., peritoneal) immune function is affected by carbon dioxide pneumoperitoneum. The production of tumor necrosis factor and the phagocytotic capacity of peritoneal macrophages are less lowered. The systemic stress response, as determined by delayed-type hypersensitivity response and leukocyte antigen expression on lymphocytes, shows a preservation of immune function after laparoscopic surgery, as compared with conventional surgery. CONCLUSIONS: Intraperitoneal carbon dioxide insufflation attenuates peritoneal immunity, but laparoscopic surgery is associated with a lower systemic stress response than open surgery.

[Shoshin beriberi provoked by the inhalation of salbutamol]. / Sjosjin-beriberi na inhalatie van salbutamol.

A 45-year-old male alcoholic with a deficient diet was given salbutamol for exertion-related dyspnoea. After inhalation, he presented with a severe dyspnoea, acrocyanosis, anuria and low blood pressure as well as a respiratory compensated lactate acidosis. Shoshin beriberi was suspected on clinical grounds. The low level of thiamine and the prompt recovery after thiamine repletion confirmed this diagnosis. Shoshin beriberi is an acute, cardiac form of beriberi, which can rapidly result in death due to cardiogenic shock and lactate acidosis. Adrenergic agents can cause a hyperdynamic circulation and thus aggravate the effects of a thiamine deficiency.